Development of Polymeric Blend Microspheres from Chitosan-Hydroxypropylmethyl Cellulose for Controlled Release of an Anti-Cancer Drug

  • Reddy, Lakshmi C. Narayana ;
  • Reddy, Rama Subba P. ;
  • Rao, Krishna K.S.V. ;
  • Subha, M.C.S. ;
  • Rao, Chowdoji K.
  • Received : 2013.01.14
  • Accepted : 2013.07.10
  • Published : 2013.08.20


Chitosan (CS) and hydroxypropylmethyl cellulose (HPMC) blend microspheres were prepared by water-in-oil emulsion technique and were loaded with an anti-cancer drug 5-fluorouracil (5-FU). CS-HPMC microspheres were characterized by Fourier transform infrared spectroscopy to confirm the cross-linking reaction. Scanning electron microscopy (SEM) was also used to assess the surface morphology of particles prepared. The quantity of release of 5-FU from the microspheres have been studied in terms of blend composition and amount of cross-linking agent. Differential scanning calorimetry and X-ray diffraction techniques indicated a uniform distribution of 5-FU particles in microspheres, whereas SEM suggested the spherical structure of the microspheres with slight rough surface. The in vitro drug release indicated that the particle size and release kinetics depend upon blend composition, amount of cross-linking agent used and amount of 5-FU present in the microspheres.


Chitosan;Hydroxypropylmethyl cellulose;Microspheres;Drug release;Anti-cancer drug


  1. Cadee, J. A.; de Groot, C. J.; Jiskoot, W.; Den Otter, W.; Hennink, W. E. Release of Recombinant Human Interleukin-2 from Dextran-Based Hydrogels. J. Control. Rel. 2002, 78, 1-13.
  2. Ryoichi, M.; Honda, R.; Takahashi, Y. Development of Oral Controlled Release Preparations, a PVA Swelling Controlled Release System (SCRS). II. In Vitro and in Vivo Evaluation. J. Control. Rel. 2000, 68, 115-120.
  3. Pillay, V.; Fassihi, R. A Novel Approach for Constant Rate Delivery of Highly Soluble Bioactives from a Simple Monolithic System. J. Control. Rel. 2000, 67, 67-78.
  4. Van, T. N.; Ng, C. H.; Aye, K. N.; Trang, T. S.; Stevens, W. F. Production of High-Quality Chitin and Chitosan from Preconditioned Shrimp Shells. J. Chem. Tech. Biotech. 2006, 81(7), 1113-1118.
  5. Miyazaki, S.; Ishi, K.; Nadai, T. The Use of Chitin and Chitosan as Drug Carriers. Chem. Pharm. Bull. 1981, 29, 3067-3069.
  6. Sawayanagi, Y.; Nambu, N.; Nagai, T. Directly Compressed Tablets Containing Chitin or Chitosan in Addition to Lactose or Potato Starch. Chem. Pharm. Bull. 1982, 30, 2935-2940.
  7. Hos, W. M.; Miyazaki, S.; Takeda, M. Sustained Release of Indomethacin from Chitosan Granules. Chem. Pharm. Bull. 1985, 33, 3986-3992.
  8. Sawayanagi, Y.; Nambu, N.; Nagai, T. Enhancement of Dissolution Properties of Prednisolone from Ground Mixtures with Chitin or Chitosan. Chem. Pharm. Bull. 1983, 31, 2507-2509.
  9. Peppas, N. A.; Khare, A. R. Preparation, Structure and Diffusional Behavior of Hydrogels in Controlled Release. Adv. Drug Delivery Rev. 1993, 11, 1-35.
  10. Cory, B.; Martin, K.; Amanda, C.; Kyekyoon, K.; Daniel, W. P. Precise Control of PLG Microsphere Size Provides Enhanced Control of Drug Release Rate. J. Control. Rel. 2002, 82, 137-147.
  11. Salsa, T.; Veiga, F.; Pina, M. E. Oral Controlled-Release Dosage Forms. I. Cellulose Ether Polymers in Hydrophilic Matrices. Drug Dev. Ind. Pharm 1997, 23, 929-938.
  12. Vazquez, M. J.; Casalderrey, M.; Duro, R.; Gomez-AJL, Martinez-PR, Souto, C. Atenlol Release from Hydrophilic Matrix Tablets with Hydroxyl Propylmethyl Cellulose (HPMC) Mixtures as Gelling Agent: Effects of Viscosity of the HPMC Mixture. Eur. J. Pharm. Sci. 1996, 4, 39-48.
  13. Campos-Aldrete, M. E.; Villafuerte-Robles, L. Influence of the Viscosity Degree and the Particle Size of HPMC on Metronidazole Release from Matrix Tablets. Eur. J. Pharm. Biopharm. 1997, 43, 173-178.
  14. Ford, J. L.; Rubinstein, M. H.; Hogan, J. E. Formulation of Sustained Release Promethazine Hydrochloride Tablets Using Hydroxypropylmethylcellulose Matrices. Int. J. Pharm. 1985, 24, 327-338.
  15. Ford, J. L.; Rubinstein, M. H.; Hogan, J. E. 1985. Propranolol Hydrochloride and Aminophylline Release from Matrix Tablets Containing Hydroxypropylmethylcellulose. Int. J. Pharm. 1985, 24, 339-350.
  16. Holgado, M. A.; Caraballo, I.; Alvarez-Fuentes, J.; Fernandez-Hervas, M. J.; Fernandez-Arevalo, M.; Rabsco, A. M. Int. J. Pharm. 1995, 118, 151.
  17. Perez-Marcos, B.; Ford, J. L.; Armstrong, D. J.; Elliott, P. N.; Rostron, C.; Hogan, J. E. Influence of pH on the Release of Propranolol Hydrochloride from Matrices Containing Hydroxypropylmethyl Cellulose K4M and Carbopol 974. J. Pharm. Sci. 1996, 85, 330-334.
  18. Tahara, K.; Yamamoto, K.; Nishihata, T. Overall Mechanism Behind Matrix Sustained Release(SR) Tablets Prepared with Hydroxypropyl Methylcellulose 2910 J. Control. Rel. 1995, 35, 59-66.
  19. Krogel, I.; Bodmeier, R. Developemnt of a Multifunctional Matrix Drug Delivery System Surrounded by an Impermeable Cylinder. J. Control. Rel. 1999, 61, 43-50.
  20. Sezer, A. D.; Akbuga, J. Comparison on In Vitro Characterization of Fucospheres and Chitosan Microspheres Encapsulated Plasmid DNA (pGM-CSF): Formulation Design and Release Characteristics. AAPS. Pharm. Sci. Tech. 2009, 10, 1193-1199.
  21. Cuna, M.; Alonso, M. J.; Torres, D. Preparation and in Vivo Evaluation of Mucoadhesive Microparticles Containing Amoxycillin-Resin Complexes for Drug Delivery to the Gastric Mucosa. Eur. J. Pharm. Biopharm. 2001, 51, 199-205.
  22. Chowdary, K. P. R.; Rao, Y. S. Design and in Vitro and in Vivo Evaluation of Mucoadhesive Microcapsules of Glipizide for Oral Controlled Release: A Technical Note. AAPS. Pharm. Sci. Tech. 2003, 4, 87-92.
  23. Krishna Rao, K. S. V.; Naidu, B. V. K.; Subha, M. C. S.; Aminabhavi, T. M. Controlled Release of Ibuprofen and Diclofenac Sodium through Beads of Alginate and Hydroxyethyl Cellulose Blends. J. Appl. Polym. Sci. 2006, 102, 5708-5718.
  24. Sudha, C. A.; Lata, S. M.; Aminabhavi, T. M. Interpenetrating Polymer Network Blend Microspheres of Chitosan and Hydroxyethyl Cellulose for Controlled Release of Isoniazid. Int. J. Bio. Macromol. 2010, 47, 171-179.
  25. Ajit, P. R.; Namdev, B. S.; Sangamesh, A. P.; Aminabhavi, T. M. Novel Interpenetrating Polymer Network Microspheres of Chitosan and Methylcellulose for Controlled Release of Theophylline. Carbohyd Polym 2007, 69, 678-687.
  26. Peppas, L. B.; Preparation and Characterization of Crosslinked Hydrophilic Networks. In Absorbent Polymer Technology; Brannon-peppas, L., Harland, R. S., Elsevier: Amsterdam, 1990; pp 45-66.
  27. Peppas, L. B.; Peppas, N. A. The Equilibrium Swelling Behavior of Porous and Non-Porous Hydrogels. In Absorbent Polymer Technology; Brannon-Peppas, L., Harland, R. S., Eds.; Elsevier: Amsterdam, 1990; pp 67-102.
  28. Siepmann, J.; Peppas, N. A.; Modeling of Drug Release from Delivery Systems Based on Hydroxypropyl Methylcellulose (HPMC). Adv. Drug. Deliv. Rev. 2001, 48, 139-157.
  29. Chowhan, Z. T. Role of Binders in Moisture-Induced Hardness Increase in Compressed Tablets and Its Effect on in Vitro Disintegration and Dissolution. J. Pharm. Sci. 1980, 69, 1-4.
  30. Lim, S. T.; Forbes, B.; Berry, D. J.; Martin, G. P.; Brown, M. B. In Vivo Evaluation of Novel Hyaluronan/Chitosan Microparticulate Delivery Systems for the Nasal Delivery of Gentamicin in Rabbits. Int. J. Pharm. 2002, 231, 73-82.
  31. Kahtani Ahmed, A. L.; Bhojya Naik, H. S.; Sherigara, B. S. Synthesis and Characterization of Chitosan-Based pHSensitive Semi-Interpenetrating Network Microspheres for Controlled Release of Diclofenac Sodium. Carbohyd. Res. 2009, 344, 699-706.